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This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects.
Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study.
Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3.
Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Cohort 1a | Experimental | Single IV dose of GSK2862277 as a continuous infusion over 2 hours. |
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| Part 1: Cohort 1b | Experimental | Single IV dose of GSK2862277 as a continuous infusion over 3 hours. |
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| Part 1: Cohort 1c | Experimental | Single IV dose of GSK2862277 as a continuous infusion over 3 hours. |
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| Part 2: Cohort 2a GSK2862277 | Experimental | Single IV dose of GSK2862277 as a continuous infusion over 1 hour. |
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| Part 2: Cohort 2a Placebo | Experimental | Matching placebo will be administered as a continuous IV infusion over 1 hour. |
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| Part 2: Cohort 2b GSK2862277 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single IV dose of GSK2862277 | Drug | GSK2862277 solution available in a 40 mg vial for IV administration. |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2 | Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study. | Up to 42 days |
| Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3 | Safety and tolerability parameters will include recording of AEs, throughout the study. | Up to 42 days |
| Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2 | Laboratory tests will include haemogram, clinical chemistry, urine examination. | Up to 42 days |
| Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3 | Laboratory tests will include haemogram, clinical chemistry, urine examination. | Up to 42 days |
| Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2 | Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature. | Up to 42 days |
| Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3 | Vital signs will include BP, heart rate respiration rate and body temperature. | Up to 42 days |
| Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 | The blood samples will be collected for plasma concentrations of GSK2862277. | Up to 48 hours post dose |
| PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Harrow | Middlesex | HA13UJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26178412 | Derived | Cordy JC, Morley PJ, Wright TJ, Birchler MA, Lewis AP, Emmins R, Chen YZ, Powley WM, Bareille PJ, Wilson R, Tonkyn J, Bayliffe AI, Lazaar AL. Specificity of human anti-variable heavy (VH ) chain autoantibodies and impact on the design and clinical testing of a VH domain antibody antagonist of tumour necrosis factor-alpha receptor 1. Clin Exp Immunol. 2015 Nov;182(2):139-48. doi: 10.1111/cei.12680. Epub 2015 Sep 11. |
| Label | URL |
|---|---|
| Results for study 116343 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 116343 | Dataset Specification | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Single IH dose of GSK2862277. |
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| Part 2: Cohort 2b Placebo | Experimental | Matching placebo will be administered. |
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| Part 3: Cohort 3a GSK2862277 | Experimental | IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days. |
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| Part 3: Cohort 3a Placebo | Experimental | Matching placebo will be administered as IV infusion over 1 hour daily for 5 days. |
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| Part 3: Cohort 3b GSK2862277 | Experimental | Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days. |
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| Part 3: Cohort 3b Placebo | Experimental | Matching placebo will be administered as IH daily for 5 days. |
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| Matching placebo single dose IV infusion | Drug | Matching placebo solution available for IV administration. |
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| Single IH dose of GSK2862277 | Drug | GSK2862277 nebulised solution available in a 40 mg vial for IH administration. |
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| Matching placebo single dose IH | Drug | Matching placebo nebulised solution available for IH administration. |
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| Repeat IV dose of GSK2862277 | Drug | GSK2862277 solution available in a 40 mg vial for IV administration. |
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| Matching placebo repeat dose IV infusion | Drug | Matching placebo solution available for IV administration. |
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| Repeat IH dose selected of GSK2862277 from Part 2 | Drug | GSK2862277 nebulised solution available in a 40 mg vial for IH administration. |
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| Matching placebo repeat dose IH | Drug | Matching placebo nebulised solution available for IH administration. |
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Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study. |
| Up to 42 days |
| Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3 | Safety data will include ECG readings obtained at each timepoint during the study. | Up to 42 days |
| Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2 | Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). | Up to 42 days |
| Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3 | Spirometry monitoring will include FEV1 and FVC. | Up to 42 days |
| Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1 | Blood samples will be collected for assessment of plasma cytokines. | Up to 42 days |
| Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 | Presence of anti GSK2862277 binding antibodies will be evaluated. | Up to 60 days |
| Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3 | Presence of anti GSK2862277 binding antibodies will be evaluated. | Up to 60 days |
The blood samples will be collected for plasma concentrations of GSK2862277. |
| Up to 48 hours post last dose |
| PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b | The blood samples will be collected for plasma concentrations of GSK2862277 | Up to 48 hours post last dose |
| PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1 | The PK parameters will be compared with historic GSK1995057 PK data in Part 1 | Up to 48 hours post last dose |
| Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2 | The pharmacodynamic and immune function biomarkers in serum. | Up to 48 hours post last dose |
| Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3 | The pharmacodynamic and immune function biomarkers in serum. | Up to 48 hours post last dose |
| Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c | IL-8 expression in ex vivo whole blood essay (WBA). | Up to 12 hours post dose |
| Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a | The urine samples will be collected for urine concentrations of GSK2862277. | Up to 48 hours post dose |
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 116343 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D055370 | Lung Injury |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
| D013898 | Thoracic Injuries |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D007262 | Infusions, Intravenous |
| ID | Term |
|---|---|
| D061605 | Administration, Intravenous |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D007263 | Infusions, Parenteral |
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